Strain dependent effects of prenatal stress on gene expression in the rat hippocampus.

Strain dependent effects of prenatal stress on gene expression in the rat hippocampus.
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DOI:
10.1016/j.physbeh.2011.02.032
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发表时间:
2011-08-03
影响因子:
2.9
通讯作者:
Leonard S
Leonard S
中科院分区:
医学3区
文献类型:
--
作者:
Neeley EW;Berger R;Koenig JI;Leonard S

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已经开发出多种动物模型来概括人类疾病精神分裂症的表型。模拟该疾病的许多认知和感觉缺陷的模型是在大鼠中使用随机变量产前应激(PS)。这些缺陷表明分子起源于海马体,海马体是一个在压力调节中发挥作用的大脑区域。为了研究产前应激母鼠后代海马基因表达的变化并解决遗传变异问题,我们在对应激具有不同反应的三种不同大鼠品系中使用了随机阵列的产前应激源:费舍尔大鼠、斯普拉格-道利大鼠和刘易斯大鼠。选择涉及压力、精神分裂症、认知、神经营养作用和免疫的候选基因,在静息条件下和短暂暴露于束缚压力后通过实时定量PCR进行评估。 PS 导致后代基因表达存在显着差异,这是菌株依赖性的。在 PS Sprague-Dawley 和 Lewis 大鼠中,N-甲基 D-天冬氨酸受体亚型 2B (Grin2b) 的 mRNA 表达增加,肿瘤坏死因子-α (Tnfα) 转录物减少,但在 Fischer 大鼠中则没有。在每个品系的所有对照大鼠中,在急性应激后,海马中脑源性神经营养因子(Bdnf)mRNA的表达增加,但在PS Sprague-Dawley和Lewis大鼠中,在急性应激后,海马中的脑源性神经营养因子(Bdnf)mRNA的表达下降。与 Lewis 或 Sprague-Dawley 大鼠相比,Fischer 品系大鼠中糖皮质激素受体 (Nr3c1) 的表达降低,但 Fischer 大鼠的 α7 烟碱受体 (Chrna7) 表达明显较高。在这些动物中观察到的表达差异可能是由于 PS 和遗传背景而观察到的表型差异的重要因素。
Multiple animal models have been developed to recapitulate phenotypes of the human disease, schizophrenia. A model that simulates many of the cognitive and sensory deficits of the disorder is the use of random variable prenatal stress (PS) in the rat. These deficits suggest a molecular origin in the hippocampus, a brain region that plays a role in the regulation of stress. To study both hippocampal gene expression changes in offspring of prenatally stressed dams and to address genetic variability, we used a random array of prenatal stressors in three different rat strains with diverse responses to stress: Fischer, Sprague-Dawley, and Lewis rats. Candidate genes involved in stress, schizophrenia, cognition, neurotrophic effects, and immunity were selected for assessment by real-time quantitative PCR under resting conditions and following a brief exposure to restraint stress. PS resulted in significant differences in gene expression in the offspring that were strain dependent. mRNA expression for the N-methyl D-aspartate receptor subtype 2B (Grin2b) was increased, and tumor necrosis factor-alpha (Tnfα) transcript was decreased in PS Sprague-Dawley and Lewis rats, but not in the Fischer rats. Expression of brain-derived neurotrophic factor (Bdnf) mRNA in the hippocampus was increased after an acute stress in all controls of each strain, yet a decrease was seen after acute stress in the PS Sprague-Dawley and Lewis rats. Expression of the glucocorticoid receptor (Nr3c1) was decreased in the Fischer strain when compared to Lewis or Sprague-Dawley rats, though the Fischer rats had markedly higher α7 nicotinic receptor (Chrna7) expression. The expression differences seen in these animals may be important elements of the phenotypic differences seen due to PS and genetic background.
DOI: 10.1111/j.1471-4159.2010.07016.x
发表时间: 2010-12-01
影响因子: 4.7
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DOI: 10.1196/annals.1300.008
发表时间: 2003-01-01
期刊: GLUTAMATE AND DISORDERS OF COGNITION AND MOTIVATION
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DOI: 10.1159/000126973
发表时间: 1996-04-01
期刊: NEUROENDOCRINOLOGY
影响因子: 4.1
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DOI: 10.1093/schbul/sbl049
发表时间: 2007-01-01
影响因子: 6.6
作者:
Braff, David L.;Freedman, Robert;Gottesman, Irving I.
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DOI: 10.1016/0896-6273(94)90159-7
发表时间: 1994-01-01
期刊: NEURON
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